Clinical Findings in Chromosome Aberrations

Oral presentation at the 5th European Cytogenetic Conference (ECC), Madrid, June 2005, organized by the European Cytogeneticists Association.
Partly reproduced from the Catalogue of unbalanced chromosome aberrations in man. A. Schinzel. Walter de Gruyter Ed

Clinical findings in chromosome aberrations

Patients with chromosome aberrations always have a distinct clinical
picture. They resemble each other as a group

Many, but not all chromosome aberrations, cause a highly distinct pattern
of abnormalities; patients with these aberrations resemble each other more
than their sibs and parents

Although there is no 'cure' for the adverse impact of chromosomal
imbalances on the phenotype (including development), early diagnosis is very
important for proper management, prognosis and avoidance of recurrence of
chromosome aberrations

Chromosome aberrations are characterised by four major criteria:

intrauterine and postnatal growth retardation

a pattern of dysmorphic signs, especially of facies, genitalia and
distal limbs

malformations, often multiple

impaired mental development/mental deficiency

Pattern of dysmorphic signs

General:

Minor anomalies

No functional importance, rather of aesthetic importance

May be found in healthy and normal individuals as well

Characteristic for a given chromosome aberration is a pattern and not a
single dysmorphism

Reflect disharmonic and/or defective early development of various anatomic
structures and allow to determine their onset during prenatal development

Partial trisomy and tetrasomy for similar segment

Tetrasomy tends to go along with more severe mental retardation and
limited survival as compared to trisomy of the same segment

Strong or less strong selection for cytogenetic examinations?

Strong selection: Chromosome examination only performed in cases with high
suspicion of a chromosome aberration

Requires continuous activities of very experienced clinical geneticists
and cytogeneticists and an optimal flow of information/good collaboration with
clinicians

Advantage: saves a lot of resources (health insurance costs);
concentration to effective and interesting work

Disadvantage: misses some highly interesting and unusual cases where
unexpectedly a chromosome aberration was found; unemployment

Prenatal Cytogenetic Diagnosis

1967 : Amniotic fluid cell culture

1984 : Chorionic villus chromosome examination

2000:

More prenatal than postnatal chromosome examinations

15% of western European pregnancies controlled

60% for advanced maternal age

Wish

Abnormal ultrasound findings

Abnormal AFP screening result

Previous child with chromosome aberration

Up to now decrease in life borns with chromosome aberration is balanced by
increasing mean maternal age (for trisomy 21 and sex chromosome aberrations);
true decrease of liveborn with trisomy 13 &18, triploidy and 4p- (due to
ultrasound)